The prevention of murine nephritis by the induction of tolerance to nucleosides isologous IgG has been extended and confirmed in a different strain of BWF1 mice. The facilitation of tolerance to DNA by cortisone is now compared with another immunosuppressive drug, Cytoxan. Unilateral nephrectomy is being performed in adult BWF1 treated with cortisone and tolerogen to judge the efficacy of treatment in the same animal. Study on the genetic of tolerance to guanosine is being carried out in two different strains of mice, Balb/c and SJL. It was found that male are more easily tolerized than female. This could explain, in part, the overwhelming incidence of SLE in female. Construction of new tolerogen such as nucleotide linked to isologous IgG is being carried out. We will attempt to induce tolerance to determinants larger than nucleosides to suppress the formation of antibody to D-DNA completely. Finally, a new study on cross tolerance to purine and pyrimidine bases is under study.